Background
Patients who become infected after stroke have worse neurological outcome than those who remain infection free. The nature of this association is unclear. We sought to determine the effects of lipopolysaccharide (LPS) administration during middle cerebral artery occlusion (MCAO) on neuropathology one month later.
Methods
Male Lewis rats were subjected to 3 hours of MCAO. At the time of reperfusion, a subset of animals was injected intraperitoneally with LPS (1 mg/kg). Animals were sacrificed at various time points after stroke for histological and immunocytochemical analysis. Temperature and behavioral outcome were monitored.
Results
Initial infarct size at 6, 24, and 72 hours did not differ between LPS(+) and LPS(−) animals. One month after MCAO, the ischemic hemispheres of LPS(+) animals were more atrophic than that of LPS(−) animals (Figure 1; P<0.05) and there were more apoptotic neurons in this hemisphere (P=0.03). LPS(+) animals also had evidence of ongoing CNS inflammation with more CD8+ cells in the ischemic hemisphere (P=0.02) and more neutrophils in the ischemic core (P=0.04).
Discussion
We show that injection of LPS 3 hours after MCAO onset leads to long-term pathological changes in the brain consistent with chronic inflammation. Exposure to inflammatory stimuli after clinical stroke may similarly enhance the CNS inflammatory response and neuronal cell death in patients, which might be expected to lead to worse clinical outcome.